Hyperlipidemia is a known risk factor in the pathogenesis of coronary artery disease. Research is proposed on laboratory animals to determine if the excretory function of the gastrointestinal tract can be utilized to deplete the body of excess lipid. Attempts will be made to cause malabsorption of fats, including cholesterol, by three basic methods. The first will be to interfere with formation of mixed bile salt micelles by adding cholestyramine and/or nonabsorbable lipid to the diet. The next approach will be to overexpand the bile salt micelles to undersaturate their capacity to solubilize lipid and thereby interfere with mucosal uptake of fats. This will be accomplished by adding conjugated bile salts and/or phospholipid to the diet. The final attempt will be to interfere with mucosal function by drug administration with either methotrexate of fenfluramine. Additionally, studies on the mucosal function of the intestine with regards to lipid absorption will be explored. Particular emphasis will be devoted to the lipid reesterifying enzymes of the endoplasmic reticulum. Attempts will be made to solubilize and purify these enzymes and to demonstrate what components of the membrane, if any, influence the activities of these enzymes. The role of membrane phospholipid will be studied in detail.